Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homogenates of cultured skin fibroblasts from a non-ambulatory, 20-year-old male with cherry-red spots, corneal clouding, seizures, mental retardation, dysostosis multiplex, dwarfism, coarse facies and loss of vision, originally described by Goldberg et al. (1971), have diminished neuraminidase activity and an excess of neuraminic acid-rich compounds. Specifically, these cells have 2-17% normal neuraminidase when measured with 2-(3' methoxyphenyl)-N-acetyl-alpha-neuraminic acid, N-acetyl-neuramin-lactose and fetuin. Activities of 12 other lysosomal enzymes were either at or above the range of normal control fibroblasts. Total neuraminic acid concentration was 44.3 nmol/mg protein versus an average control value of 14.2. It is concluded that the Goldberg syndrome should be considered, along with mucolipidosis I and the cherry-red spot -- myoclonus syndrome, as resulting from a primary neuraminidase deficiency.
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PMID:Neuraminidase deficiency in the original patient with the Goldberg syndrome. 51 4

The authors performed galactose loading tests in children suffering from chronic diseases: recurrent bronchitis vomiting, diarrhoea, milk-intolerance, somatic and mental retardation, cramps. In 32 of the 92 examined cases galactose levels rose until pathological, pseudo- diabetic levels. Stillbirth, cataract, hyperbilirubinaemia, convulsions occurred among family members of 10 patients. Galactose-1-phosphat-uridyl-transferase levels were decreased only in 4 of the 17 patients examined. In the other cases some different pathway of galactose metabolism is suspected. Complete remission of symptoms was achieved with diet devoid of milk sugar (lactose) in 29 patients: one infant died and two others remained mentally retarded. According to the examinations presented minor deviations of galactose metabolism cause clinical symptoms more frequently in early life as it was supposed until now.
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PMID:[Galactose loading test in infants and small children suffering in recurrent bronchitis and other chronic illness (author's transl)]. 611 85

Two siblings with classic transferase deficiency galactosemia that was detected at birth have been treated with lactose restriction since the neonatal period. Both patients developed a unique and progressive neurologic syndrome of mental retardation, tremor, and ataxia. Careful review of the family history and medical records, the absence of metabolic disturbances other than those related to galactosemia, and the aggregate physical findings and neurodiagnostic studies ruled out other neurologic disorders in these siblings. It is therefore proposed that these patients represent a subgroup of transferase-deficient galactosemic patients, who develop characteristic neurologic sequelae with conventional dietary management. The existence of this subgroup should be considered in evaluations of therapeutic responses in cohorts of patients with galactosemia. Further, galactosemia should be included in the differential diagnosis of tremor and ataxia in the setting of mental retardation.
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PMID:Curious neurologic sequelae in galactosemia. 670 Oct 54

Inherited deficiencies of UDP-galactose 4-epimerase (GALE) have been associated with two distinct phenotypes. The vast majority of North American patients are clinically asymptomatic, are identified through newborn screening programmes for classical galactosaemia, and are of African-American descent. At least two symptomatic patients have been reported, one Pakistani and the other Asian Muslim, both with severe complications in the neonatal period and subsequent mental retardation. Through newborn screening, we have identified a GALE-deficient patient who is of mixed Pakistani/caucasian ancestry. He was clinically well in the neonatal period on a lactose-containing diet, and biochemical studies, including urine reducing sugars and galactitol, were consistent with a diagnosis of peripheral GALE deficiency. Although early developmental milestones were met normally, he now shows significant developmental delays in both motor and language skills. Mutational analysis revealed this patient to be a compound heterozygote at the GALE locus, with mutations N34S and L183P identified in the patient and confirmed in the parents. This report represents the first characterization of specific mutations in a GALE-deficient patient in conjunction with biochemical and clinical phenotype, and facilitates further studies of the GALE enzyme and its role in the different clinical forms of epimerase-deficiency galactosaemia.
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PMID:Molecular characterization of a unique patient with epimerase-deficiency galactosaemia. 970 May 91

Galactosemia is an autosomal recessive disease related to deficiency of one of three different enzymes involved in the metabolism of galactose: galactokinase (GALK), galactoso-J-phosphate uridyltransferase (GALT) or UDP-galactose-4-epimerase (GALE). Classic galactosemia is due to GALT deficiency and is the most common. Longitudinal studies have shown that in spite of early diagnosis and early treatment of children with galactosemia detected in the mass screening programme, the results are poor and mental retardation as well as other complications are of similar severity as in children diagnosed clinically without screening. In many investigations it was also proved that some impairments developed already in the prenatal period. Therefore, many countries among them also Poland, stopped mass screening for galactosemia. At present, in Poland the procedure strategy in galactosemic children and their families include: diagnosis of new cases on the basis of clinical symptoms, selective screening in high-risk families, prophylactic lactose-free diet for mothers during pregnancy. Such management can help to prevent clinical manifestations in newborns and prevent death in the early period of life.
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PMID:[Effectiveness of the screening programme for galactosemia. New strategy in Poland]. 1127 4

This paper focuses on the influence of maternal nutrition on infant survival and growth and on subsequent fertility. During pregnancy, modifications in the maternal hormonal system help maintain availability of nutrients to the fetus relatively independently of maternal nutrition. When maternal dietary deficiencies reach critical levels, the effectiveness of these mechanisms in maintaining fetal nutrition decreases. Studies have confirmed the correlation of severe maternal malnutrition and lowered birth weight, neurological disorders, impaired physical growth, mental retardation, and poor school performance. Marginal nutritional status affects milk production capacity. The basis of most recommendations for lactating mothers is that the average mother produces 850 ml of milk each day. Depending on the anticipatory reserves of fat from pregnancy still available and the level of physical activity of the mother, from 2750 to 3300 Kcal/day may be needed. When the mother's energy intake is good, milk fat resembles that of her dietary fat, but when there is a shortage of food energy, the milk fatty acid pattern resembles the mother's subcutaneous fat stores. The lactose content and overall protein content of milk seem stable despite changes in the maternal diet, but the vitamin content, particularly water soluble vitamins, is very sensitive to dietary intake. Birth weight has consistently been found to be associated with infant mortality through 2 main mechanisms: maternal malnutrition may lead to a smaller placental size and decreased nutrient supply to the fetus, resulting in developmental retardation during intrauterine life, or maternal malnutrition may result in suboptimal lactation performance which will contribute to malnutrition and growth retardation of the child. Maternal nutritional status has an independent effect on the duration of postpartum amenorrhea. Improving maternal diet without concurrently introducing contraception may shorten the birth interval and consequently elevate the birthrate.
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PMID:Maternal nutrition, infant health, and subsequent fertility. 1226 49

Thyroid dysfunctions can produce reproductive problems. Untreated maternal hypothyroidism has serious consequences on development of offspring, resulting in stunted growth and mental retardation. The effects of propylthiouracyl-induced hypothyroidism (0.1 g l(-1) in drinking water starting 8 days before mating, or given to virgin rats for 30 or 50 days) on the serum profiles of hormones related to reproduction and mammary function (prolactin, growth hormone (GH), progesterone, corticosterone, oestradiol, insulin-like growth factor I (IGF-I), thyroid-stimulating hormone (TSH), triiodothyronine and tetraiodothyronine), and on mammary function in virgin, pregnant and lactating rats, were investigated. Propylthiouracyl treatment severely decreased circulating triiodothyronine and tetraiodothyronine concentrations, and increased serum TSH concentrations. Virgin rats showed prolonged periods of vaginal dioestrus, increased circulating progesterone concentrations and afternoon peaks of prolactin concentration, which are indicative of prolactin-induced pseudopregnancy. Propylthiouracyl-treated virgin rats had mammary development comparable to that of midpregnancy, and half of these rats had increased mammary casein and lactose concentrations. Serum prolactin concentrations were decreased on the afternoon of day 5 of pregnancy, increased during late pregnancy (days 15-21) and were normal during lactation. Circulating GH concentrations decreased on days 15-21 of pregnancy, whereas progesterone concentrations increased during late pregnancy and early lactation. Circulating oestradiol (measured in late pregnancy and in virgin rats), IGF-I and corticosterone concentrations were decreased. Although assessment of mammary histology showed no differences in extent of development, casein content was increased in propylthiouracyl-treated rats on day 21 of pregnancy; litter growth was severely reduced and at day 20 of age the pups were hypothyroid, with decreased GH serum concentrations. An acute suckling experiment was performed on days 10-12 of lactation to determine whether some impairment in mammary function or the suckling reflex might account for these differences. After an 8 h separation of mothers from their litters and 30 min of suckling, circulating prolactin values were not affected by propylthiouracyl treatment, but serum oxytocin concentration and milk excretion were reduced. In conclusion, hypothyroidism induces various alterations in the hormone profiles of virgin and pregnant rats, and induces pseudopregnancies and mammary development in virgin rats. These alterations do not appear to have an overt impact on the outcome of pregnancy and on mammary function during lactation, with the exception of the milk ejection reflex, which may account at least partially for the reduced litter growth.
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PMID:Effect of hypothyroidism on hormone profiles in virgin, pregnant and lactating rats, and on lactation. 1296 45

Multiple cases with various types of pediatric malabsorption syndromes were evaluated. The clinical manifestations, laboratory findings, pathophysiology, and histopathological descriptions of each patient were analyzed in an effort to clear the pathogenesis of the malabsorption syndromes and the treatments were undertaken. The cases studied, included one patient with cystic fibrosis, two with lactose intolerance with lactosuria (Durand type), one with primary intestinal lymphangiectasia, two with familial hypobetalipoproteinemia, one with Hartnup disease, one with congenital chroride diarrhea, one with acrodermatitis enteropathica, one with intestinal nodular lymphoid hyperplasia (NLH), five with intractable diarrhea of early infancy and four with glycogenosis type Ia. Each case description and outcome is described below: 1. A 15-year-old Japanese boy with cystic fibrosis presented with severe symptoms, including pancreatic insufficiency, bronchiectasis, pneumothorax and hemoptysis. His prognosis was poor. Analysis of the CFTR genes of this patient revealed a homozygous large deletion from intron 16 to 17b. 2. In the sibling case of Durand type lactose intolerance, the subjects'disaccaridase activity of the small bowel, including lactase, were within normal limits. The results of per oral and per intraduodenal lactose tolerance tests confirmed lactosuria in both. These observations suggested, not only an abnormal gastric condition, but also duodenal and intestinal mucosal abnormal permeability of lactose. 3. In the case of primary intestinal lymphangiectasia, the subject had a lymphedematous right arm and hand, a grossly coarsened mucosal pattern of the upper gastrointestinal tract (identified via radiologic examination) and the presence of lymphangiectasia (confirmed via duodenal mucosal biopsy). The major laboratory findings were hypoalbuminemia, decreased immunoglobulin levels and lymphopenia resulting from loss of lymph fluid and protein into the gastro-intestinal tract. 4. In two cases of heterozygous familial hypobetalipoproteinemia, serum total cholesterol and betalipoprotein levels were very low. The subjects presented with symptoms and signs of acanthocytosis and fat malabsorption. Further, one subject had neurological abnormalities such as mental retardation and severe convulsions. Treatment with MCT formula diet corrected the lipid malabsorption. 5. A 5-year-old girl presented with pellagra-like rashes, mental retardation and cerebellar ataxia. An oral tryptophan (Trp) and dipeptide (Trp-Phe) loading test were conducted and the renal clearance of amino acids was also evaluated in this patient and in controls. Following the oral Trp loading test, plasma levels of Trp indicated a lower peak in the case, reaching a maximum at 60 minutes. On the other hand, the oral dipeptide (Trp-Phe) loading test in the Hartnup patient showed the peak Trp plasma level was the same as the control subjects. The renal clearance of neutral amino acids in this case increased to levels 5 to 35 times normal. 6. In the case of congenital chloride diarrhea, the subject had secondary lactose intolerance, dehydration, hyponatremia, hypokalemia, hypochloremia, hyperreninemia and metabolic alkalosis. The chloride content of her fecal fluid was very high. The concentrations were 89-103 mEq/l. In contrast, her urine was chloride-free. The subject's growth and development improved after treatment with lactose free formura and oral replacement of the fecal loses of water, NaCl and KCl. Unfortunately, the patient died of a small bowel intussusception. The kidney histopathological finding was juxtaglomerular hyperplasia by a necropsy. 7. In the case of acrodermatitis enteropathica, the subject had characteristic skin lesions, low serum zinc levels and ALPase activity. An oral ZnSO4 loading test and intestinal mucosal histology by a peroral biopsy were conducted. The serum zinc peak level was 2 hours after the oral ZnSO4 loading test. Infant formula alone could not maintain normal serum zinc ranges. Light microscopic studies of the intestinal villous architecture showed a normal pattern. However, ultrastructual examination of several epithelial cells revealed numerous intracellular vesicles. After zinc therapy, these changes were decreased. The lesions were postulated as the secondary result of zinc deficiency. 8. A 12-year-old girl presented with hypogammaglobulinemia, recurrent infections, chronic diarrhea and intestinal NLH. A barium meal and follow-through examination showed multiple nodules throughout the stomach and intestine. The nodules, all uniform in size, were 2 mm diameter. The barium enema did not show NLH in the colon. Mucosal biopsy of the stomach and jejunum revealed the typical histology of NLH in the lamina propria. Also, achlorhydria was present in this patient and her serum gastrin levels were very high; 315-775 pg/ml. 9. In 4 cases of intractable diarrhea in early infancy (by Avery G B), a jejunal biopsy showed shortening villi and nonspecific enterocolitis. Some patients were found with only low lactase or low lactase and sucrase levels. An electron microscope analysis of the small bowel in 2 cases showed alterations: increased pinocytosis in microvillus membranes and lysosomes by endocytosis of undigested macromolecular substances. I postulated that the stated evidence was causative of this clinical profile. 10. I frequently observed diarrhea as a clinical manifestation in glycogenosis type Ia and lipid malabsorption in one case. The light and electron photomicrographs showed intestinal absorption cells with the glycogen deposits in the inferior devision of nuclei.
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PMID:[Clinical studies of pediatric malabsorption syndromes]. 1722 86

Substrate deprivation therapy has been successfully applied in a number of lysosomal storage diseases, such as Gaucher disease. So far only limited experience is available in Sandhoff disease. We initiated substrate deprivation therapy in one male patient, who initially presented at the age of 3.5 years with epilepsy and regression in motor skills and speech development. Juvenile Sandhoff disease was diagnosed on the basis of a decreased hexosaminidase activity in leukocytes and a homozygous HEXB gene mutation. After the epilepsy was controlled, the clinical course remained stable for years, defined by a mild proximal myopathy and stable mental retardation. At 14 years of age the patient experienced a second episode with progressively worsening general condition with diminishing muscle power and progressive ataxia. Treatment was started with the N-alkylated imino sugar miglustat, inhibiting the glucosylceramide synthase, an essential enzyme for the synthesis of glycosphingolipids. Diarrhoea was treated with lactose restriction. We performed detailed biochemical investigations, motor and mental development analysis, brain imaging, organ function studies and quality of life score prior to and at different time points after start of the treatment. Two years after the initiation of therapy the patient has a stable neurological picture without further regression in his motor development, ataxia or intelligence. There is a subjective improvement in the fine motor skills and walking up the stairs but no change in the quality of life score. Under treatment with miglustat the clinical course in our patient with Sandhoff disease did not further deteriorate.
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PMID:Substrate deprivation therapy in juvenile Sandhoff disease. 1989 52